German Pat. No. 1,545,725 (and related but not identical Klingler U.S. Pat. No. 3,398,150) as well as German OS No. 2 136 643 (and related Klingler U.S. Pat. No. 3,728,346) among other matters disclose a process for the production of compounds of the general formula ##STR4## wherein Alk is a straight or branched chain alkylene group with 3 to 4 carbons and R is hydrogen or an alkyl group with 1 to 6 carbon atoms by catalytic hydrogenation of ketones of the general formula ##STR5## wherein the phenolic hydroxyl groups and/or the basic secondary nitrogen atoms can be protected by a benzyl.
The entire disclosures of the two Klingler United States patents are hereby incorporated by reference and relied upon.
The hydrogenation is carried out in water, methanol, ethanol or water-alcohol mixture.
A great disadvantage in the hydrogenation of such compounds, however, is that it is necessary to work in great dilution since the starting ketones have extremely low solubility. If, for example, there is used a starting ketone of formula (B) in which the secondary basic nitrogen atom has a benzyl group as a protective group, in the hydrogenation first this benzyl group is split off so that the nearly insoluble ketone which is formed very frequently precipitates out in the reaction vessel even at elevated temperatures and high dilutions and the catalyst surface is thereby so inactivated that then the already only difficultly hydrogenatable keto group is only reduced extremely slowly and incompletely. The described disadvantages are particularly noticeable in technical and production scale operations.
As can be seen, for example, from German Pat. No. 1,545,725 in the hydrogenation of ketones of formula (B) (Examples 1, 2, 6 and 7) there is needed 25 to 72 times the amount of solvents in the form of mixtures. Even if there should be used dimethyl formamide (not disclosed in the German patent) which is exceptionally suitable for catalytic hydrogenation of difficultly soluble substances the preliminary product of Example 2, for example, must be dissolved in 15 times the amount of this solvent. However, at the optimum temperatures of 60.degree. to 70.degree. C. for this reaction there precipitates out under these conditions the debenzylated ketone (B) as a result of which the further hydrogenations, particularly in large scale operations, becomes extremely difficult. In the necessary hydrogenation times of about 48 hours there arise colored by-products and the still strongly ketone containing final product formed must be post hydrogenated to obtain the required purity for pharmaceutical use and must be recrystallized with attendant substantial loss of product. A large scale production in this manner therefore is very expensive and uneconomical.